(Philadelphia, PA) - Researchers at the University
of Pennsylvania School of Medicine have established
in an animal model that the hormone adiponectin secreted
by fat tissue acts in the brain to reduce body weight.
In contrast to leptin, a related hormone, adiponectin
can cause weight loss by raising metabolic rate while
not affecting appetite. This finding may have future
implications in understanding and treating obesity and
metabolic disorders like diabetes, says lead author,
Rexford Ahima, MD, PhD, Assistant Professor
of Medicine, Penn Diabetes Center. This research appears
in the May issue of Nature Medicine.

When adiponectin, which is involved in glucose and lipid
metabolism, was introduced into the cerebrospinal fluid
of normal mice, they showed no changes in food intake,
but their metabolism rose. “The animal burns off
more heat, so over time loses weight, which was very
fascinating because we knew that leptin caused weight
loss by suppressing appetite and increasing metabolic
rate,” explains Ahima. “Here we have another
fat hormone that can cause weight loss but without affecting
intake.”

For many dieters, it’s easy, at first, to lose
weight; but over time, it becomes more difficult because
the body compensates, in part, by dropping its metabolic
rate. “Adiponectin or its targets in the brain
and other organs could be harnessed to sustain weight
loss by maintaining a high metabolic rate,” says
Ahima. “This is only a possibility. We’re
not suggesting at this point that adiponectin will become
a drug.” In severely obese mice, adiponectin rapidly
decreases blood glucose and lipids, while burning fat.
Hence, adiponectin could be beneficial in the treatment
of diabetes and heart disease associated with obesity.

These findings have far-reaching potential to help fight
the war against obesity, which healthcare experts agree
has reached epidemic proportions in the United States.
“For years people used to think fat tissue was
a passive player--just there to store excess energy,”
explains Ahima. This proved to be a simplistic view
since hormones produced by fat tissue are released into
the blood and are actively involved in the regulation
of metabolism. The best known fat hormone, leptin, decreases
body weight by decreasing appetite and increasing metabolic
rate. Leptin also reduces glucose and lipids. The researchers
found that both adiponectin and leptin require the melanocortin
pathway in the brain to control body weight and glucose.
However, these fat hormones also control metabolism
through other distinct pathways in the brain. “We
focus on the brain because it is a major coordinator
of feeding, metabolism, and hormones, including insulin,”
says Ahima.

Other Penn researchers collaborating on this work are
Yong Qi, Nobuhiko Takahashi, and Hiralben R. Patel,
as well as Philipp E. Scherer, Anders Berg, and Utpal
B. Pajvani from the Albert Einstein College of Medicine
and Stanley M. Hileman from West Virginia University.
The research is funded by grants from the National Institutes
of Health.

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